Antimigraine 4-pyrimidinyl and pyridinyl derivatives of indol-3yl-alkylpiperazines

Abstract

A series of novel alkoxypyridin-4-yl and alkoxypyrimidin-4-yl derivatives of indol-3-ylalkylpiperazines of Formula I are intended to be useful agents he on the basis of their potent affinity and agonist activity at 5-HT1D binding sites.

We claim: 
     
       1. A compound of Formula IB or pharmaceutically acceptable acid addition salts and hydrates thereof ##STR19## wherein R 2  is selected from hydrogen, halogen, lower alkyl, lower alkoxy and --CO 2  R 9  ; R 3  and R 7  are independently selected from hydrogen and lower alkyl;   R 4  is lower alkyl;   R 5  and R 6  are independently selected from hydrogen and lower alkyl, or R 5  and R 6  may be combined as a methylene or ethylene bridge;   R 8  is selected from hydrogen, lower alkyl, R 7  -substituted phenyl-lower alkyl, and trifluoromethyl;   R 9  is selected from lower alkyl and R 7  -substituted phenyl-lower alkyl;   R 10  is selected from --OCH 2  CONR 7  R 8 , --O 2  CR 9 , --O 2  CNR 7  R 8 , --SO 2  NR 7  R 8 , --SO 2  R 9 , --COR 8 , --CO 2  R 9 , --NR 7  SO 2  R 9 , --NR 7  CO 2  R 9 , --NR 7  COR 8 , and ##STR20## and n is selected from zero and the integers 1 and 2.   
     
     
       2. The compound of claim 1 wherein R 10  is selected from the group consisting of --SO 2  NR 7  R 8  and --SO 2  R 9 . 
     
     
       3. A method for preventing vascular headaches, consisting of migraine and cluster headaches, by administering a prophylactically effective amount of a claim 1 compound to a person at risk of suffering the onset of a vascular headache. 
     
     
       4. The compound of claim 1 wherein R 10  is selected from the group consisting of --OCH 2  CN, --OCH 2  CONR 7  R 8 , --O 2  CR 9  and --O 2  CNR 7  R 8 . 
     
     
       5. The compound of claim 1 wherein R 10  is selected from the group consisting of --COR 8 , and --CO 2  R 9 . 
     
     
       6. The compound of claim 1 wherein R 10  is selected from the group consisting of --NR 7  SO 2  R 9 , --NR 7  CO 2  R 9 , --NR 7  COR 8  and ##STR21## 
     
     
       7. The compound of claim 2, wherein R 10  is --SO 2  NR 7  R 8 . 
     
     
       8. The compound of claim 7, 4-(5-Methoxy-4-pyridinyl)-1-[3-[5-[[(methylamino)sulfonyl]methyl]-1H-indol-3-yl]propyl]piperazine. 
     
     
       9. A pharmaceutical composition in unit dosage form suitable for systemic administration to a person at risk of or suffering vascular headache, the composition comprising a pharmaceutical carrier and from about 1 to 500 mg of a claim 1 compound. 
     
     
       10. A method for treating vascular headaches, consisting of migraine and cluster headaches, by administering a therapeutically effective amount of a claim 1 compound to a person suffering from the vascular headache.